Dordaviprone/ONC201 Activation of the ClpP Mitochondrial Protease Inhibits the Growth of KRAS-Mutant Pancreatic Cancer and Overcomes RAS Inhibitor Resistance
ClpP activation by dordaviprone/ONC201 suppressed PDAC cell growth and overcame resistance to the RAS(ON) multi-selective inhibitor RMC-7977, providing support for investigating this combination as a potential combination treatment for KRAS-mutant pancreatic cancer.
Authors
- Seamus Degan (ORCID: https://orcid.org/0000-0002-8028-2081)
- Clint A. Stalnecker (ORCID: https://orcid.org/0000-0002-0570-4416)
- Adrienne D. Cox (ORCID: https://orcid.org/0000-0002-4901-2454)
- Wen-Hsuan Chang (ORCID: https://orcid.org/0000-0002-5751-6345)
- Kristina Drizyte‐Miller (ORCID: https://orcid.org/0000-0001-7049-2934)
- Emanuel F. Petricoin (ORCID: https://orcid.org/0000-0001-9146-5572)
- Elisa Baldelli (ORCID: https://orcid.org/0000-0002-6288-4599)
- Edwin J. Iwanowicz
- Ryan D. Mouery (ORCID: https://orcid.org/0000-0002-1866-1742)
- Jeffrey A. Klomp (ORCID: https://orcid.org/0000-0002-5243-6987)
- Channing J. Der (ORCID: https://orcid.org/0000-0002-7751-2747)
- Runying Yang (ORCID: https://orcid.org/0000-0002-5983-9439)
- Kirsten L. Bryant (ORCID: https://orcid.org/0000-0003-4026-0942)
- Brandon L. Mouery (ORCID: https://orcid.org/0000-0002-8900-3413)
- Amber M. Amparo (ORCID: https://orcid.org/0000-0003-3805-746X)
- Lee M. Graves (ORCID: https://orcid.org/0000-0002-4736-9855)
- Sheila R. Nicewarner Peña (ORCID: https://orcid.org/0009-0001-9917-577X)
Institutions
- University of North Carolina at Chapel Hill (US)
- George Mason University (US)
- Madera BioSciences (United States) (US)
- Michigan State University (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2025-12-03
- DOI
- https://doi.org/10.64898/2025.12.01.691471
- Primary Topic
- Protein Kinase Regulation and GTPase Signaling
- Type
- article
- Field-Weighted Citation Impact
- 0.00